Ischemic stroke and diabetes: a TLR4-mediated neuroinflammatory perspective

Ischemic stroke is the major contributor to morbidity and mortality in people with diabetes mellitus. In ischemic stroke patients, neuroinflammation is now understood to be one of the main underlying mechanisms for cerebral damage and recovery delay. It has been well-established that toll-like receptor 4 (TLR4) signaling pathway plays a key role in neuroinflammation. Emerging research over the last decade has revealed that, compared to ischemic stroke without diabetes mellitus, ischemic stroke with diabetes mellitus significantly upregulates TLR4-mediated neuroinflammation, increasing the risk of cerebral and neuronal damage as well as neurofunctional recovery delay. This review aims to discuss how ischemic stroke with diabetes mellitus amplifies TLR4-mediated neuroinflammation and its consequences. Additionally covered in this review is the potential application of TLR4 antagonists in the management of diabetic ischemic stroke.